The application of big data to the quality assurance of radiation therapy is multifaceted. Big data can be used to detect anomalies and suboptimal quality metrics through both statistical means and more advanced machine learning and artificial intelligence. The application of these methods to clinical practice is discussed through examples of guideline adherence, contour integrity, treatment delivery mechanics, and treatment plan quality. The ultimate goal is to apply big data methods to direct measures of patient outcomes for care quality. The era of big data and machine learning is maturing and the implementation for quality assurance promises to improve the quality of care for patients.